Purpose: To report the results of treating resistant bacterial keratitis by corneal collagen cross-linking followed by therapeutic penetrating keratoplasty and to compare with those of therapeutic penetrating keratoplasty alone. Methods: Retrospective analysis of the medical records of 33 eyes of 33 patients diagnosed with resistant bacterial keratitis. Fourteen eyes (14 patients) were treated with photoactivated chromophore for infectious keratitis corneal collagen cross-linking (PACK-CXL) followed by therapeutic penetrating keratoplasty (TPK) (group I) and 19 eyes (19 patients) were treated by TPK alone (group II). The main outcome measures were graft clarity and the mean best corrected visual acuity at 1, 3, 6, 12 and 18 months after penetrating keratoplasty. Results: The mean age of the patients was 53.6 ± 1.9 years and 52.3 ± 1.8 years in group I and group II, respectively (p = 0.374), the mean ulcer size was 49.9 ± 16.2 mm2 and 54.7.1 ± 15.1 mm2 in group I and group II, respectively (p = 0.239), the mean corneal infiltrate size was 58.2 ± 17mm2 and 59.9 ± 15.7 mm2 in group I and group II, respectively (p = 0.384). Hypopyon was seen in 6 eyes (41.7%) in group I and in 8 eyes (42.1%) in group II. At the last follow-up visit, 12 corneal grafts (85.7%) maintained their clarity in group I while 13 corneal grafts (68.4%) maintained their clarity in group II (p = 0.037) and the mean best corrected visual acuity was 0.84 ± 0.63 log MAR in group I and 1.27 ± 0.81 log MAR in group II (p = 0.024). Postoperatively, one eye (7%) showed graft reinfection in group I that was controlled medically while 5 eyes (26.3%) showed resistant graft reinfection and ended in graft opacification in group II (p = 0.042). Conclusion: In resistant bacterial keratitis, priming infected corneas with PACK-CXL before performing TPK improve the results in such cases